1. Field of the Invention
The present invention relates to novel hydantion derivatives and more particularly (d)-6-fluoro-2,3-dihydro-2',5'-dioxo-spiro-[4H-1-benzopyran-4,4'-imidazoli dine]-2-carboxamide derivative, a process for the preparation thereof, and use thereof as an agent for preventing and curing chronic complications due to diabetes.
2. Related Arts
Hitherto, various studies have been made for finding out an effective agent to cure diabetes, which can be orally administered. As a result, various agents therefor, each of which comprises as an effective ingredient, sulfonyl urea, mesooxalate or guanidine derivatives or the like have been developed and marketed but those are of a mere symptomatic treating agent to a hyperglycoplasmia due to the diabetes, specific chronic complications such as diabetic cataract, diabetic neuropathy, diabetic retinopathy and the like, but there is almost no effective agent for preventing and curing the complications and thus it may be said no effective therapeutic system has been established.
Therefore, various studies have also been made for developing an effective agent for preventing and curing such intractable diseases due to diabetes but it is the fact that there is almost no success case. As one of the studies, there is a search on inhibition substance to an aldose reductase, since the enzyme reduces in vivo of human and other animals, aldose such as glucose and galactose into corresponding polyols such as sorbitol and galactitol and it has been known that said complications will appear when the formed sorbitol and galactitol are accumulated at crystalline lens, peripheral nerve, kidney or the like in patients of diabetes or galactosemia ["Jap. J. Opthalmol.", Vol. 20, page 399 (1976); "Int. Congr. Ser. Excerpta Med.", Vol. 403, page 594 (1977); and "Metabolism", Vol. 28, page 456 (1979)].
Various compounds having the inhibition activity to the aldose reductase have hitherto been reported and the present inventors have also found that (d)-6-fluoro-2,3-dihydro-2',5'-dioxo-spiro[4H-1-benzopyran-4,4'-imidazolid ine]-2-carboxamide of the following formula shows a remarkable activity of inhibition to the aldose reductase in vitro and vivo tests, in comparison with other agents [Jap. Pat. Nos. Sho 63-57588 (A) and 63-126881 (A) equivalent to U.S. Ser. No. 07/090729 filed Aug. 28, 1987 (now U.S. Pat. No. 4,861,792) and European Pat. Publn. No. 0264586 (A1)]. ##STR2##